This proposed study examines the effect of a recently initiated population-level biomedical intervention- expanded universal and free of cost highly active antiretroviral therapy (HAART)-on HIV risk behaviors among a high-risk population, men who have sex with men (MSM), in British Columbia (BC), Canada. Of particular interest is whether the efficacy of expanded HAART access as an HIV prevention measure might be negated by socio-cultural/bio-behavioral factors, including risk compensation or "HAART optimism" within the MSM communities. The majority of new HIV infections in BC occur among MSM and this has remained largely unchanged since the year 2003 with approximately 200 new infections each year. The preventive value of HAART has been highlighted and the BC Ministry of Health has massively increased funding to expand access to HAART as a strategy to reduce the number of new HIV infections in the province. BC HIV treatment guidelines have also been relaxed so that HAART is available to almost all HIV-infected individuals in the province. Approximately 40% of persons who die from HIV-related causes in BC do not receive ART prior to death and approximately 27% of HIV-infected individuals may be unaware of their HIV status. This major expansion of access to HAART constitutes a population-level biomedical intervention-a rare, natural experiment-thereby creating an opportunity to examine the impact of expanded HAART access on complex determinants of HIV risk behaviors at the individual level. Over the 5-year study period, we propose to use respondent driven sampling (RDS) to recruit a cohort of 270 HIV-positive and 410 HIV-negative MSM (680 in total) aged 16 years and older, and follow them up every 6 months for a median of four years. We propose to use RDS for its strength in recruiting deeply from hidden and diverse populations. Our main aims are to 1) examine trends in sexual risk behavior and attitudes regarding the preventive value of HAART over a 4.5-year period as the numbers of MSM on HAART dramatically increase and the concept of HAART as prevention becomes widely diffused;2) examine how self-reported drug-use before and during sex explains HIV sexual risk behavior;and 3) examine the interactions between soft and hard drug use, HAART optimism and treatment adherence and continuation among HIV-positive MSM receiving HAART. All study participants will be asked to sign a consent form, complete a questionnaire using Computer Assisted Self-Interview technology, and undergo a rapid HIV test, syphilis test, hepatitis C serology, urine and anal swab screens for N. gonnorhea and Chlamydia trachomatis and to provide consent to allow researchers access to health services databases in the province. All HIV-positive individuals not already accessing regular HIV care will be linked to local healthcare providers for regular medical care and for assessment of need for HAART. PUBLIC HEALTH RELEVANCE: The province-wide biomedical intervention of HAART as HIV prevention initiated in British Columbia, Canada is a natural experiment that offers a unique opportunity to observe how a population level HIV intervention would unfold when relatively unaffected by cost barriers or lack of access to health care. It offers a unique natural laboratory for the focused research proposed here to examine how behavioral and socio-cultural factors and drug use interact to contribute to the relative success or shortfall of treatment as prevention, as implemented by the provincial government program. The data we propose to collect will facilitate detecting risk compensatory behavior and changes in attitudes, beliefs and cultural norms to provide insight to policy makers and program planners for responsive prevention initiatives. The data will identify important determinants of success for implementing or evaluating treatment as prevention initiatives in comparable jurisdictions in Canada and the United States. The results of this study will also be of great value for designing better quality, culturally competent sexual and healthy-living services for HIV-positive MSM that support their right to be sexually active and achieve their goals in life.